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Energetics of ligand binding to activate site of glutathione transferase M1-1Kinsley, Nichole Michelle 14 November 2006 (has links)
Student Number : 0002483R -
MSc dissertation -
School of Molecular and Cell Biology -
Faculty of Science / Isothermal titration calorimetry was used to investigate the forces that drive ligand
binding to the active site of rGST M1-1. In an attempt to gain insight into the
recognition of non-substrate ligands by GSTs, this study also investigates interactions
between rGST M1-1 and ANS, a non-substrate ligand. At 25 °C, complex formation
between rGST M1-1 and GSH, GSO3
-, and S-hexylglutathione is characterised by a
monophasic binding isotherm with Kd values of 38.5 mM, 2.1 mM and 0.2 mM,
respectively. One molecule of each ligand is bound per monomer of rGST M1-1.
Binding of these ligands is enthalpically favourable and entropically unfavourable
with a resultant favourable Gibbs free energy, overall. The effects of temperature and
buffer ionisation on the energetics of binding were studied. The enthalpic and
entropic contributions for all three ligands exhibited temperature dependence over the
temperature range investigated (5-30 °C). The Gibbs free energy showed negligible
changes with increasing temperature due to enthalpy-entropy compensation. The
temperature dependence of the binding enthalpy yielded heat capacity changes of –
2.69 kJ/mol/K and –3.68 kJ/mol/K at 25 °C for GSH and S-hexylglutathione binding
and –1.86 kJ/mol/K overall for GSO3
-. The linear dependence of DH on temperature
for GSO3
- binding to rGST M1-1 suggests the formation of a more constrained
complex which limits the fluctuations in conformations of the mu-loop at the active
site. The non-linear dependence of DH on temperature for GSH and Shexylglutathione
binding to the enzyme suggests the formation of a complex that
samples different bound conformations due to the mobility of the mu-loop even after
ligand is bound. Calorimetric binding experiments in various buffer systems with
different ionisation enthalpies suggest that the binding of GSH to rGST M1-1 is
coupled to the deprotonation of the thiol of GSH while GSO3
- binding to rGST M1-1
is independent of the buffer ionisation. At 25 °C, the rGST M1-1#1;ANS association is
represented by a monophasic binding isotherm with one molecule of ANS bound per
monomer of rGST M1-1. The interaction is both enthalpically and entropically driven
with a Kd value of 27.2 mM representing moderate affinity. The effect of temperature
on the interaction was investigated over the temperature range of 5-30 °C. The linear
dependence of the binding enthalpy on temperature indicates that no significant
structural changes occur upon binding of ANS to the enzyme (DCp = -0.34 kJ/mol/K).
The change in heat capacity associated with the interaction can be attributed to the burial of the polar sulphonate group of ANS and the exposure of the anilino and
naphthyl rings to solvent as well as the possibility of weak electrostatic interactions
between ANS and residues at the active site. The effect of ethacrynic acid, GSH,
GSO3
- and S-hexylglutathione on the fluorescence of ANS was investigated in order
to obtain some idea as to the location of the ANS binding site on rGST M1-1. ANS
was displaced by GSO3
-, S-hexylglutathione and ethacrynic acid, while no
displacement occurred upon binding of GSH to the active site of rGST M1-1.
Displacement studies and molecular docking simulations indicate that ANS binds to
the H-site of rGST M1-1 and the possibility of a second binding site for the molecule
cannot be ruled out.
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Hurricane Katrina : utilization of private, non-governmental health professionals time for new strategiesScott, Linda J. 09 1900 (has links)
CHDS State/Local / This thesis focuses on the medical as part of the public health response to Hurricane Katrina, specific to the issues of the private, non-governmental health professional. A brief survey was completed by 39 state level Bioterrorism Hospital Coordinators. Information obtained highlights the issues of the inability to deploy these private health professionals. Traditional governmental mutual aid mechanisms do not cover private non-governmental health professionals for workers compensation and death benefits. A review of the potential deployment mechanisms provides insight to the challenges and complexity specific to private health professionals. The motivation for volunteerism highlights the importance of targeting volunteer activities to the motivation of the individual volunteer. Investigating the impact thwarting the private, nongovernmental health professionals may have on future planning and response activities reinforce the need to modify the structures currently in place. The National Response Plan stresses the importance of including private industry into emergency preparedness and response strategies. This thesis outlines a strategy to pilot a project working with an established state volunteer registry by providing mechanisms to federalize those pre-identified, pre-credentialed volunteer health professionals. Once completed, this pilot could be expanded to other states ensuring a solid mechanism to quickly and safely mobilize this critical response discipline. / Bioterrorism Hospital Coordinator, Michigan Department of Community Health
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Regulation of Disclosure and Corporate Governance: An Empirical Investigation of Economic ConsequencesMüller-Bloch, Stephanie 22 September 2016 (has links)
No description available.
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Sharing the Wealth: Movement Toward Gender Parity in Managerial & Professional Specialty Occupations from 1950 to 1980Jolly, D. Leeann 01 December 1986 (has links)
Data on the managerial and professional specialty occupations that were specified by the United States Census of the Population for the years 1950 through 1980 were used to analyze the influence of occupational sex ratios, growth rates, and male and female salary levels on the ability of females to move into those occupations. An analysis of the change in the Standardized Occupational Sex Ratio (SSR) showed that, over the thirty year period studied, growth rates became more important than salary levels in influencing movement toward parity in high status occupations.
Before the 1980 census year, occupational growth rates were found to interact with both male and female salary levels. During all four census years, slowly growing occupations experienced the smallest movement toward parity regardless of salary level. The lack of movement toward parity in slowly growing occupations shows evidence of gender division. In rapidly growing fields, lower salary levels for both males and females led to greater movement toward parity for females. Movement toward parity in rapidly growing fields that offered lower salaries was taken as evidence of less sheltering. In declining fields, occupations with above median female salaries allowed greater female entry than did those with below median female salaries. The opportunity for women to move into declining fields showed evidence of chain mobility.
By 1980, females were moving into managerial and professional specialty occupations at every salary level and growth rate; however, the greatest movement toward parity occurred in those occupations that were rapidly growing. Movement toward parity in rapidly growing occupations provided evidence of structural mobility. By 1980, rapidly growing occupations were experiencing fair sharing of occupational opportunity. The slowly growing occupations, though experiencing some female growth, still showed evidence of male sheltering.
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An Investigation of the Impact of Corporate Governance on Decision to Expense Employee Stock OptionsJiang, Ling 01 January 2006 (has links)
Corporations have the choice of expensing (using the fair value method), or non-expensing (using the intrinsic value method and provide pro forma disclosure in financial statement footnotes) of employee stock options. The current study examines how corporate governance factors affect such choices. Prior studies (Xie et al. 2003; Klein 2002; Peasnell et al. 2000) have indicated that certain corporate governance factors have an impact on corporate accounting behavior, including earnings management. Based on the assumption that expensing employee stock options is a good practice of accounting that improves earnings quality, it is hypothesized that these corporate governance factors would affect companies' option expensing decisions, in ways similar to how they affect companies' other earnings management choices.A series of hypotheses relating to specific corporate governance factors are developed. These corporate governance factors include: Board independence (percentage of independent directors on the board, CEO/board chairman split, and tenure of independent directors), board expertise (governance expertise and financial expertise), board diligence, board ownership, board size, CEO tenure, and internal blockholders (cumulative ownership percentage of internal blockholders, and whether the largest blockholder is the CEO). A sample of firms that elected to expense employee stock options up to early September 2003 is identified from the report of Bear, Stearns & Co., Inc. (2003), and a control sample of non-expensing firms is selected based on certain matching principles. The final sample consists of 235 expensing firms and 235 matched control firms, 470 firms in total.A logit regression is conducted. The dependent variable is companies' decisions on whether or not to expense employee stock options. The independent variables are corporate governance factors and control variables. Regression results indicate that the following corporate governance factors have statistically significant impact on option expensing decisions in the directions predicted: finance expertise, board diligence, and whether the CEO is the largest blockholder. Regression results indicate a statistically significant impact on option expensing decisions, which is in the opposite direction than predicted, for the cumulative ownership percentage of internal blockholders. The impacts of all other corporate governance factors are statistically insignificant.
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Orthodontic Faculty Recruitment and Retention: Goals and PerceptionsPeck, Sheldon L 01 January 2003 (has links)
There is a shortage of faculty in academic dentistry and orthodontics in particular. The purpose of this study was to quantify real and perceived differences in income, workload, and satisfaction between full-time academic and private practice orthodontists. Surveys were returned by 119 (70%) faculty, 79 (36%) private practitioners, and 160 (59%) orthodontic residents. Average annual income for faculty was less than half that of private practitioners. Faculty also reported working significantly more hours per week and taking less vacation time. Though both faculty and practitioners perceived their own jobs to be more satisfying overall, faculty felt academics was more stressful, involved more bureaucracy, and made it more difficult for them to obtain ABO certification. Residents reported educational debt averaging $132,120 and perceived it would take nearly twice as long to pay off in an academic career. Only residents felt that faculty were more respected than their private practice colleagues.
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Latency and Distortion compensation in Augmented Environments using Electromagnetic trackersHimberg, Henry 17 December 2010 (has links)
Augmented reality (AR) systems are often used to superimpose virtual objects or information on a scene to improve situational awareness. Delays in the display system or inaccurate registration of objects destroy the sense of immersion a user experiences when using AR systems. AC electromagnetic trackers are ideally for these applications when combined with head orientation prediction to compensate for display system delays. Unfortunately, these trackers do not perform well in environments that contain conductive or ferrous materials due to magnetic field distortion without expensive calibration techniques. In our work we focus on both the prediction and distortion compensation aspects of this application, developing a “small footprint” predictive filter for display lag compensation and a simplified calibration system for AC magnetic trackers. In the first phase of our study we presented a novel method of tracking angular head velocity from quaternion orientation using an Extended Kalman Filter in both single model (DQEKF) and multiple model (MMDQ) implementations. In the second phase of our work we have developed a new method of mapping the magnetic field generated by the tracker without high precision measurement equipment. This method uses simple fixtures with multiple sensors in a rigid geometry to collect magnetic field data in the tracking volume. We have developed a new algorithm to process the collected data and generate a map of the magnetic field distortion that can be used to compensation distorted measurement data.
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CEO Characteristics and the Choice of Using Non-Financial Performance Measures in Compensation ContractsSimerly, Melloney C, Ph.D. 01 January 2015 (has links)
This study examines how CEO characteristics influence the decision to use non-financial performance measures (NFPM) in compensation contracts. Specifically, I examine the CEO characteristics: gender, age, tenure, risk-aversion, overconfidence, and sensitivity of wealth. Using trait theory and the extant literature examining NFPM, females, age, tenure, and risk-aversion are expected to be positively associated with the use of NFPM while competing hypotheses are presented for overconfidence and sensitivity of wealth. Employing a two-way fixed effects method, controlling for fixed effects at the firm and year level, I find that female CEOs are positively associated with the use of NFPM because of increased risk-aversion. The short-term horizon perspective of younger and older CEOs lead to less preference for NFPM. Increasing tenure is associated with the power to self-select into contracts that include NFPM. Moreover, tenure is incrementally more important than age and gender. The results for overconfidence are inconclusive. Finally, risk-aversion and sensitivity of wealth are both positively associated with weight of NFPM. The results of this study further the understanding for the use of NFPM and provide information regarding the specific managerial fixed effects that influence compensation decisions.
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Development and Validation of a Predictive Model of Return-to-Work Outcomes of Injured Employees in MinnesotaHankins, A. Bentley 01 January 2013 (has links)
In Minnesota’s workers’ compensation system, injured employees at risk for sustaining permanent disability may be eligible for receipt of vocational rehabilitation (VR) services if they are determined to be capable of benefitting from such services. VR services can be a valuable resource to injured employees who need assistance minimizing their work disability and maximizing their residual wage-earning capacity. However, for VR services to be effective at a system level, it is necessary to precisely and accurately identify an injured employee’s rehabilitation potential. Failure to do so is likely to result in the misallocation of a scarce and costly resource. Given recent trends in Minnesota’s workers’ compensation system (e.g., higher VR service costs and lower RTW rates among injured employees with indemnity claims), this study was conducted with the purpose of developing and validating an objective, evidence-based method of predicting the RTW status as of claim closure of injured Minnesota employees who sustained permanent impairment and received VR services. To accomplish this purpose, a closed-claim, retrospective design was implemented. Data for this cross-sectional study was obtained from the Minnesota administrative claims database. There were 15,372 claims that met all eligibility criteria. With guidance from the biopsychosocial disablement models developed by Nagi and the World Health Organization, 15 discrete predictor variables that represented medical, individual, and workplace factors were selected for study inclusion. Descriptive and predictive analyses were used to assess the relationship between this study’s RTW outcome and its set of RTW predictors. Using logistic regression, an optimal RTW model was first developed and then internally validated with a split-dataset approach. The optimal RTW model included four main effects (attorney involvement; severity of permanent impairment; age; job tenure) and three first-order interaction effects (pre-injury average weekly wage X pre-injury industry; attorney involvement X severity of permanent impairment; attorney involvement X job tenure). Though not retained in the optimal RTW model, part of body affected and education also had notable bivariate relationships with the outcome. The optimal RTW model’s performance regarding goodness-of-fit and clinical usefulness suggests it may be of value to those assessing rehabilitation potential within Minnesota’s workers’ compensation system.
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Omezení vlastnického práva k pozemkům z důvodů ochrany životního prostředí / Land ownership restrictions and environmental protectionPapež, Filip January 2015 (has links)
The topic of this diploma thesis has got an interdisciplinary character, which results from a conflict of property right and ecological rights. The crucial point is the internal and external ownership restriction differentiation. This gives the answer to the question whether a compensation for restriction is provided or not. The thesis deals with legal reasons of the restrictions that arise from the specific character of land and also with the typology of restrictions according to its establishment. Selected restrictions regulated by particular environmental laws and the Building Code are analysed in the main part of the thesis. The conclusion points out the imperfections of legislation and provides possible solutions as well.
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